Two Clinical management trial protocol proposals are included in The Duke/University of Arizona AsthmaNet Center. The adult asthma management trial will assess the role of TNF-alpha antagonists in improving asthma control in obese subjects who remain on control after optimization of pharmacotherapy and treatment of co-morbidities. The pediatric asthma management trial will test the hypothesis that azithromycin, a macrolyte, can be used at the first symptoms of acute asthma exacerbation to prevent such exacerbations, and if this preventive effect is specific for carriers of a genotype in a polymorphism in IL8 (IL8/-159 AA), which we have shown is associated with increased risk of neutrophilic exacerbations. We also propose two brief concept proposals: one in which we will test for the presence of steroid resistance in obese asthmatic subjects, and a second one in which we will determine the effect of myrisolated alanine-rich kinase substrate (MARCKS)-related peptide, which is a potential regulator of mucus secretion, in improving asthma control. Finally, we propose a clinical research skills development core plan that will use the many clinical, genetic and biological and training resources available in both our clinical research units to provide training opportunities for pulmonary and allergy fellows and other trainees in the design and implementation of clinical trials in a network setting. This proposal is leveraged on the complementary strengths on the Duke Asthma Center and the Arizona Respiratory Center in the areas of severe adult asthma and childhood asthma, respectively. The Duke Asthma Center has pioneered work in the cellular and molecular biology of asthma using invasive methods to obtain airway samples, whereas the Arizona Respiratory Center is a leader in the genetics and pharmacogenetics of asthma. Both teams have extensively participated in previous NHLBI-funded asthma networks, and they have access to large populations of both children and adults with asthma of a wide range of severities. These strategies, together with our demonstrated capacity to work effectively in collaborative environments, are unique contributions that the Duke/University of Arizona AsthmaNet Center can make to the AsthmaNet initiative.